White Matter Lesions Grade Research Articles

Comparing the imaging characteristics of middle-aged patients with multiple sclerosis and CADASIL: A retrospective cross-sectional study

BackgroundFew studies have quantitatively analyzed the imaging disparities between multiple sclerosis (MS) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We aimed to compare the imaging characteristics of MS and CADASIL in middle-aged patients. Materials and MethodsThis retrospective study used a single-center database and included patients aged 40–60 years with MS and CADASIL who underwent the designated imaging protocol including 3D T1-weighted imaging and fluid attenuated inversion recovery (FLAIR), diffusion tensor imaging and susceptibility-weighted imaging between January 2018 and March 2023. Patients with MRI-detected macrobleeds were excluded. ResultsA total of 27 patients with MS (mean age, 46.7 years ± 4.4, 8 men) and 30 patients with CADASIL (mean age, 51.6 years ± 5.8, 14 men) were included. No significant differences were observed in the Fazekas grades of white matter lesions (WMLs). Patients with CADASIL exhibited greater external capsule involvement (56.7% vs.18.5 %; p = 0.006), whereas the MS group had more lesions in the corpus callosum (81.5% vs. 53.3 %, p = 0.02) and brainstem (74.1% vs. 46.7 %, p = 0.04). The CADASIL group exhibited a higher incidence of microbleeds (12.07 vs. 0.11, p = 0.001). The WMLs in the MS group exhibited a lower T1 lesion/cerebrospinal fluid signal index (2.206 vs. 2.882, p < 0.001). A value of ≤2.57 demonstrated a sensitivity of 92.6 % and a specificity of 90.0 % in differentiating MS. Patients with MS had a thinner corpus callosum (7.18 mm vs 7.86 mm, p = 0.04), while patients with CADASIL showed significantly higher mean diffusivity (0.8776 × 10–3 vs. 0.7637 × 10–3 mm2/s, p = 0.03) and lower fractional anisotropy (0.7581 vs. 0.8389, p = 0.04) in the splenium of the corpus callosum. ConclusionMiddle-aged patients with MS and CADASIL showed comparable Fazekas grades for WMLs. However, lesion distribution, T1 signal characteristics, and splenic diffusivity changes can help differentiate between MS and CADASIL.

Risk Stratification Tool for Ischemic Stroke: A Risk Assessment Model Based on Traditional Risk Factors Combined With White Matter Lesions and Retinal Vascular Caliber.

Objective: This study aims to establish a risk assessment model based on traditional risk factors combined with the Fazekas classification of white matter lesions and retinal vascular caliber for screening the patients at high risk of ischemic stroke.Methods: This study included 296 patients (128 cases of ischemic stroke and 168 cases in the normal control group). The basic data of the patients were collected. Color fundus photography was performed after pupil dilation, and the retinal vascular caliber was measured using semiautomated vascular measurement software (IVAN Software, Sydney, Australia). The severity of white matter lesions (WML) on cranial nuclear magnetic fluid-attenuated inversion recovery images were assessed using the Fazekas scale. Moreover, logistic regression analysis was used to establish different risk assessment models for ischemic stroke. The effects of models were evaluated through the receiver operating characteristic (ROC) curve and the Delong test compared area under the curve.Results: The sensitivity and specificity of models 1 (the traditional risk factor model), 2 (the retinal vascular caliber model), 3 (the WML model), and 4 (the combined the traditional risk factor, WML and central retinal artery equivalent (CRAE) model) were 71 and 55%, 48 and 71%, 49 and 67%, and 68 and 68.5% with areas under the curve of 0.658, 0.586, 0.601, and 0.708, respectively. The area under the receiver operating characteristic curve in models 1, 2, 3, and 4 showed statistically significant differences. Moreover, no statistical significance exists in the pairwise comparison of other models.Conclusion: The risk assessment model of ischemic stroke combined with Fazekas grade of WML and CRAE is superior to the traditional risk factor and the single-index model. This model is helpful for risk stratification of high-risk stroke patients.

White Matter Lesions and Outcomes After Endovascular Treatment for Acute Ischemic Stroke: MR CLEAN Registry Results.

Cerebral white matter lesions (WMLs) have been associated with a greater risk of poor functional outcome after ischemic stroke. We assessed the relations between WML burden and radiological and clinical outcomes in patients treated with endovascular treatment in routine practice. We analyzed data from the MR CLEAN Registry (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands)—a prospective, multicenter, observational cohort study of patients treated with endovascular treatment in the Netherlands. WMLs were graded on baseline noncontrast computed tomography using a visual grading scale. The primary outcome was the score on the modified Rankin Scale at 90 days. Secondary outcomes included early neurological recovery, successful reperfusion (extended Thrombolysis in Cerebral Infarction ≥2b), futile recanalization (modified Rankin Scale score ≥3 despite successful reperfusion), and occurrence of symptomatic intracranial hemorrhage. We used multivariable logistic regression models to assess associations between WML severity and outcomes, taking the absence of WML on noncontrast computed tomography as the reference category. Of 3180 patients included in the MR CLEAN Registry between March 2014 and November 2017, WMLs were graded for 3046 patients and categorized as none (n=1855; 61%), mild (n=608; 20%), or moderate to severe (n=588; 19%). Favorable outcome (modified Rankin Scale score, 0–2) was achieved in 838 patients (49%) without WML, 192 patients (34%) with mild WML, and 130 patients (24%) with moderate-to-severe WML. Increasing WML grades were associated with a shift toward poorer functional outcome in a dose-dependent manner (adjusted common odds ratio, 1.34 [95% CI, 1.13–1.60] for mild WML and 1.67 [95% CI, 1.39–2.01] for moderate-to-severe WML; Ptrend, <0.001). Increasing WML grades were associated with futile recanalization (Ptrend, <0.001) and were inversely associated with early neurological recovery (Ptrend, 0.041) but not with the probability of successful reperfusion or symptomatic intracranial hemorrhage. An increasing burden of WML at baseline is associated with poorer clinical outcomes after endovascular treatment for acute ischemic stroke but not with the probability of successful reperfusion or symptomatic intracranial hemorrhage.

The Complexity of Blood Pressure Fluctuation Mediated the Effects of Hypertension on Walking Speed in Older Adults.

Background: Older adults with hypertension often had diminished walking performance. The underlying mechanism through which hypertension affects walking performance, however, has not been fully understood. We here measured the complexity of the continuous systolic (SBP) and diastolic (DBP) blood pressure fluctuation, grade of white matter lesions (WMLs), and cognitive function and used structural equation modeling (SEM) to examine the interrelationships between hypertension, BP complexity, WMLs, cognitive function, and walking speed in single- and dual-task conditions.Methods: A total of 152 older adults with age > 60 years (90 hypertensive and 62 normotensive participants) completed one MRI scan of brain structure, a finger BP assessment of at least 10 min, Mini-Mental State Examination (MMSE) to assess cognitive function, and 10-meter walking tests in single (i.e., normal walking) and dual tasks (i.e., walking while performing a serial subtraction of three from a random three-digit number). The grade of WMLs was assessed using the total score of Fazekas scale; the complexity of SBP and DBP was measured using multiscale entropy (MSE), and the walking performance was assessed by walking speed in single- and dual-task conditions.Results: As compared to normotensives, hypertensive older adults had significantly slower walking speed, lower complexity of SBP and DBP, greater grade of WMLs, and poorer cognitive function (p < 0.03). Those with lower BP complexity (β > 0.31, p < 0.003), greater WML grade (β < −0.39, p < 0.0002), and/or poorer cognitive function (β < −0.39, p < 0.0001) had slower walking speed in single- and/or dual-task conditions. The SEM model demonstrated significant total effects of hypertension on walking speed, and such effects were mediated by BP complexity only, or BP complexity, WML grade, and cognitive function together.Conclusion: This study demonstrates the cross-sectional association between the complexity of continuous beat-to-beat BP fluctuation, WML grade, cognitive function, and walking speed in hypertensive and normotensive older adults, revealing a potential mechanism that hypertension may affect walking performance in older adults through diminished BP complexity, increased WML grade, and decreased cognitive function, and BP complexity is an important factor for such effects. Future longitudinal studies are warranted to confirm the findings in this study.

Multiscale Dynamics of Blood Pressure Fluctuation Is Associated With White Matter Lesion Burden in Older Adults With and Without Hypertension: Observations From a Pilot Study

Background: White matter lesions (WMLs) are highly prevalent in older adults, and hypertension is one of the main contributors to WMLs. The blood pressure (BP) is regulated by complex underlying mechanisms over multiple time scales, thus the continuous beat-to-beat BP fluctuation is complex. The association between WMLs and hypertension may be manifested as diminished complexity of BP fluctuations. The aim of this pilot study is to explore the relationships between hypertension, BP complexity, and WMLs in older adults.Method: Fifty-three older adults with clinically diagnosed hypertension and 47 age-matched older adults without hypertension completed one MRI scan and one BP recording of 10–15 min when sitting quietly. Their cerebral WMLs were assessed by two neurologists using the Fazekas scale based on brain structural MRI of each of their own. Greater score reflected higher WML grade. The complexity of continuous systolic (SBP) and diastolic (DBP) BP series was quantified using multiscale entropy (MSE). Lower MSE reflected lower complexity.Results: Compared to the non-hypertensive group, hypertensives had significantly greater Fazekas scores (F > 5.3, p < 0.02) and lower SBP and DBP complexity (F > 8.6, p < 0.004). Both within each group (β < −0.42, p < 0.01) and across groups (β < −0.47, p < 0.003), those with lower BP complexity had higher Fazekas score. Moreover, complexity of both SBP and DBP mediated the influence of hypertension on WMLs (indirect effects > 0.25, 95% confidence intervals = 0.06 – 0.50).Conclusion: These results suggest that diminished BP complexity is associated with WMLs and may mediate the influence of hypertension on WMLs. Future longitudinal studies are needed to examine the causal relationship between BP complexity and WMLs.

Relationship of White Matter Lesions with Intracerebral Hemorrhage Expansion and Functional Outcome: MISTIE II and CLEAR III

Intracerebral hemorrhage (ICH) patients commonly have concomitant white matter lesions (WML) which may be associated with poor outcome. We studied if WML affects hematoma expansion (HE) and post-stroke functional outcome in a post hoc analysis of patients from randomized controlled trials. In ICH patients from the clinical trials MISTIE II and CLEAR III, WML grade on diagnostic computed tomography (dCT) scan (dCT, < 24h after ictus) was assessed using the van Swieten scale (vSS, range 0-4). The primary outcome for HE was > 33% or > 6mL ICH volume increase from dCT to the last pre-randomization CT (< 72h of dCT). Secondary HE outcomes were: absolute ICH expansion, > 10.4mL total clot volume increase, and a subgroup analysis including patients with dCT < 6h after ictus using the primary HE definition of > 33% or > 6mL ICH volume increase. Poor functional outcome was assessed at 180days and defined as modified Rankin Scale (mRS) ≥ 4, with ordinal mRS as a secondary endpoint. Of 635 patients, 55% had WML grade 1-4 at dCT (median 2.2h from ictus) and 13% had subsequent HE. WML at dCT did not increase the odds for primary or secondary HE endpoints (P ≥ 0.05) after adjustment for ICH volume, intraventricular hemorrhage volume, warfarin/INR > 1.5, ictus to dCT time in hours, age, diabetes mellitus, and thalamic ICH location. WML increased the odds for having poor functional outcome (mRS ≥ 4) in univariate analyses (vSS 4; OR 4.16; 95% CI 2.54-6.83; P < 0.001) which persisted in multivariable analyses after adjustment for HE and other outcome risk factors. Concomitant WML does not increase the odds for HE in patients with ICH but increases the odds for poor functional outcome. http://www.clinicaltrials.gov trial-identifiers: NCT00224770 and NCT00784134.

Decreased Cerebrospinal Fluid Aβ42 in Patients with Idiopathic Parkinson's Disease and White Matter Lesions.

Cerebral small vessel disease (SVD), often manifesting as white matter lesions (WMLs), and Parkinson's disease (PD) are common disorders whose prevalence increases with age. Vascular risk factors contribute to SVD, but their role in PD is less clear. The study objective was to investigate the frequency and grade of WMLs in PD, and their association with clinical and biochemical parameters. In total, 100 consecutive patients with available magnetic resonance imaging were included. Vascular risk factors including smoking, hypertension, diabetes type 2, atrial fibrillation, heart insufficiency and hypercholesterolemia were assessed. In 50 patients that had underwent lumbar puncture, cerebrospinal fluid (csf) levels of beta-amyloid1-42, tau and phospho-tau were measured. WMLs were present in 86 of 100 patients. Increasing WML severity was independently associated with increased age and lower csf beta-amyloid1-42. In our study, WMLs were very common in patients with PD, and were associated with low levels of csf beta-amyloid1-42. Longitudinal studies would increase understanding of the interplay between WMLs and amyloid pathology in PD.

Deep White Matter Lesions Are Associated with Early Recognition of Dementia in Alzheimer's Disease.

Neuroimages of cerebral amyloid-β (Aβ) accumulation and small vessel disease (SVD) were examined in patients with various types of cognitive disorders using 11C-labeled Pittsburgh Compound B-positron emission tomography (PiB-PET) and magnetic resonance imaging (MRI). The mean cortical standardized uptake value ratio (mcSUVR) was applied for a quantitative analysis of PiB-PET data. The severity of white matter lesions (WML) and enlarged perivascular spaces (EPVS) on MRI were assessed to evaluate complicating cerebral SVD using semiquantitative scales. In homozygous apolipoprotein E ɛ3/ɛ3 carriers, the incidence of more severe WML and EPVS was higher in PiB-positive than PiB-negative patients, indicating that WML and EPVS might be associated with enhanced Aβ accumulation. An association study between PiB-PET and MRI findings revealed that higher WML grades significantly correlate with lower mcSUVRs, especially in the frontal area, indicating that more severe ischemic MRI findings are associated with milder Aβ accumulation among patients with Alzheimer's disease. In these patients SVD may accelerate the occurrence of cognitive decline and facilitate early recognition of dementia.

Chronic kidney disease and poor outcomes in ischemic stroke: is impaired cerebral autoregulation the missing link?

BackgroundChronic kidney disease increases stroke incidence and severity but the mechanisms behind this cerebro-renal interaction are mostly unexplored. Since both vascular beds share similar features, microvascular dysfunction could be the possible missing link. Therefore, we examined the relationship between renal function and cerebral autoregulation in the early hours post ischemia and its impact on outcome.MethodsWe enrolled 46 ischemic strokes (middle cerebral artery). Dynamic cerebral autoregulation was assessed by transfer function (coherence, phase and gain) of spontaneous blood pressure oscillations to blood flow velocity within 6 h from symptom-onset. Estimated glomerular filtration rate (eGFR) was calculated. Hemorrhagic transformation (HT) and white matter lesions (WML) were collected from computed tomography performed at presentation and 24 h. Outcome was evaluated with modified Rankin Scale at 3 months.ResultsHigh gain (less effective autoregulation) was correlated with lower eGFR irrespective of infarct side (p < 0.05). Both lower eGFR and higher gain correlated with WML grade (p < 0.05). Lower eGFR and increased gain, alone and in combination, progressively reduced the odds of a good functional outcome [ipsilateral OR = 4.39 (CI95% 3.15–25.6), p = 0.019; contralateral OR = 8.15 (CI95% 4.15–15.6), p = 0.002] and increased risk of HT [ipsilateral OR = 3.48 (CI95% 0.60–24.0), p = 0.132; contralateral OR = 6.43 (CI95% 1.40–32.1), p = 0.034].ConclusionsLower renal function correlates with less effective dynamic cerebral autoregulation in acute ischemic stroke, both predicting a bad outcome. The evaluation of serum biomarkers of renal dysfunction could have interest in the future for assessing cerebral microvascular risk and relationship with stroke complications.

White matter lesions reduce number of brain metastases in different cancers: a high-resolution MRI study.

Brain metastases are major complications of common cancers. Tumor type and proneness to the CNS are thought to define the number and size of brain metastases. It is not known if intrinsic vascular factors can also have an effect. Restricted perfusion due to cerebral small vessel disease is frequent in elderly patients and causes white matter lesions (WML). The aim of this analysis was to evaluate a possible negative effect of WML and patient age on the number and size of brain metastases (BM) of different tumor entities. Pre-therapeutic 3T brain magnetic resonance imaging (MRI) of 200 patients with BM were analyzed. Location, size and number of BM (NoM) were determined. T2 hyperintensive WML were scored according to Fazekas-Score (grade I-III). Patients with WML grade 1 (NoM: 5.59; p = 0.009) and grade 2 (NoM: 3.68; p = 0.002) had significantly less BM than patients without WML (NoM: 6.99). This effect was present in subgroups of different tumors: NSCLC (p = 0.05), other tumors than NSCLC (p = 0.048). Age (≤65 or >65 years) was positively correlated with the degree of WML but not with number (pNoM = 0.832) or mean diameter (pmDM = 0.662) of brain metastases. While patient age did not appear to be relevant, increasing WML were associated with lower number of brain metastases in different tumor types.

Significance of Cerebral Small-Vessel Disease in Acute Intracerebral Hemorrhage.

The significance of structural changes associated with cerebral small-vessel disease (SVD), including white matter lesions (WML), lacunes, and brain atrophy, to outcome from acute intracerebral hemorrhage is uncertain. We determined associations of computed tomographic radiological manifestations of cerebral SVD and outcomes, and in terms of any differential effect of early intensive blood pressure-lowering treatment, in the large-scale Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). We graded WML (van Swieten scale), the presence of lacunes, and brain atrophy (2 linear measurements and visual rating) for 2069 of 2839 patients with available baseline brain computed tomography (<6 hours of intracerebral hemorrhage onset) by 3 independent neurologists blind to clinical data. WML grade and 2 linear measurements of brain atrophy were associated with death or major disability at 90 days: multivariable-adjusted odds ratios for WML (grade 3 and 4 versus 0), frontal ratio, and third ventricle Sylvian fissure distance (most versus least severe atrophy quartile) were 1.42 (95% confidence interval, 1.02-1.98), 1.47 (1.08-1.99), and 1.64 (1.21-2.22), respectively (all P for trend <0.05). There was no association between lacunes and outcomes. There were no significant differences in the effects of intensive blood pressure-lowering across subgroups of cerebral SVD. Preexisting cerebral SVD manifestations of WML and brain atrophy predict poor outcome in acute intracerebral hemorrhage. There is no apparent hazard of early intensive lowering of blood pressure according to the INTERACT2 protocol, in patients with underlying cerebral SVD. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00716079.

Abstract WMP85: Significance of Cerebral Small Vessel Disease in Acute Intracerebral Hemorrhage: The INTERACT2 Study

Background: Uncertainty exists over the significance of structural changes arising from cerebral small vessel disease (CSVD), including white matter lesions (WML), lacunes and atrophy, for outcome after acute intracerebral hemorrhage (ICH). We determined associations of CT markers of CSVD and outcomes among participants of the INTERACT2 study. Methods: We graded WML (van Swieten scale), brain atrophy (two linear measurements, frontal ratio [FR] and third ventricle Sylvian fissure distance [TSD]) and the presence of lacunes for 2069/2839 patients with available baseline brain CT (&lt;6hr ICH onset) by three independent neurologists blind to clinical data. Results: WML and brain atrophy were independently associated with death or disability (modified Rankin Scale score 3-6) at 90 days: adjusted odds ratios for WML (grade 3 and 4 vs. 1), FR and TSD (most vs. least severe atrophy quartile) were 1.42 (95% confidence interval 1.02-0.98), 1.47 (1.08-1.99) and 1.64 (1.21-2.22), respectively (all P for trend &lt;0.05). There was no association between lacunes or any CSVD biomarkers and absolute ICH growth, and no significant differences in the effects of intensive BP lowering in each subgroup of CSVD. Conclusions: CSVD manifestations of WML and brain atrophy have prognostic value in acute ICH but they do not appear to influence ICH growth. Intensive BP lowering provided similar treatment effects irrespective of degree of CSVD.

Cerebral white matter lesions and microcirculation retinal in stroke lacunar

Background: The blood vessels in the retina are available for viewing in a noninvasive way and have similar anatomical, physiological as features small vessel brain. Also the white matter lesions (WMLs) brain are most frequently associated with lacunar stroke Objective: To determine the relationship between cerebral white matter lesions and retinal microvascular alteration in lacunar stroke. Material and methods: Cross-sectional study, patients with acute stroke was evaluated. Arteriovenous crossings, focal or diffuse arteriolar narrowing, retinal hemorrhages, cotton wool spots, alteration in vascular path, microaneurysms, the presence of retinal microvascular abnormalities was assessed. The WMLs were evaluated with a ranking of 1 to 9. Lacunar Stroke was classified by the score of TOAST. Results: A total of 67 patients were evaluated, classified as lacunar stroke 23.88% (n:16), the average age was 70.06 years, 50% were men, the main risk factors hypertension 68.75%, hypercholesterolemia 50%, diabetes 31.25%. In reference to the degree of WMLs grade 4-9 was superior to no lacunar stroke with 68.75% vs. 56.86%, the presence of retinopathy was also higher in lacunar stroke with 68.75% vs. 52.94%, but we found the presence of retinopathy in patients without diabetes and hypertension. Conclusion: WMLs and altering of retinal microcirculation are more prevalence in patients with lacunar stroke. Likewise, the retinopathy may be present in these patients despite not having recognized cardiovascular risk factors.

Endothelial dysfunction is associated with the severity of cerebral small vessel disease

The pathogenesis of cerebral small vessel disease, a disease that involves white matter lesions (WMLs) and cerebral microbleeds (CMBs), is thought to be associated with endothelial dysfunction. Flow-mediated dilation (FMD) has been used to measure endothelium-dependent vasodilation. The aim of this study was to investigate the association between endothelial function (as measured by FMD) and cerebral small vessel disease. Patients with a history of cerebrovascular disease and comorbidities were enrolled in this study (n=102; 69 males, 70.1±9.2 years). The patients were divided into two groups according to the severity of WMLs, which were assessed by Fazekas classification; grades 0 to 1 as mild WMLs group and grades 2 to 3 as severe WMLs group. A gradient-echo MRI was performed in 96 patients (94.1%) to evaluate whether CMBs were present. The patients in the severe WMLs group (n=40) were older (P=0.001), more frequently exhibited hypertension (P=0.045) and diabetes mellitus (P=0.026) and possessed lower FMD values (P<0.001) than the patients in the mild WMLs group (n=62). CMBs were observed in 30 patients (31.3%). Using receiver operating characteristic curves, the optimal FMD cutoff values for predicting the presence of severe WMLs and CMBs were 3.9% and 3.7%, respectively. On multivariate logistic analysis, FMD <4.0% (odds ratio 9.50; 95% confidence interval 3.55-28.83) was independently associated with severe WMLs. Additionally, FMD <3.8% (5.82; 2.23-16.50) was also associated with the presence of CMBs. Endothelial dysfunction as evaluated by FMD may be predictive of the severity of cerebral small vessel disease.

Factors Associated with Brain Atrophy Estimated with Automatic Voxel- Based Morphometry of Structural Magnetic Resonance Images in Elderly Diabetic Patients: Impact of Albuminuria on Hippocampal Atrophy

Background: We investigated what factors were associated with brain atrophy in elderly patients with type 2 diabetes. Methods: We evaluated hippocampal and whole brain atrophy with automatic voxel-based morphometry of structural magnetic resonance image (MRI), voxel-based specific analysis regional analysis for Alzheimer’s disease (VSRAD), in 70 diabetic subjects and 35 non-diabetic subjects. Cognitive function tests – MMSE, word recall (immediate and delayed), Digit Symbol Substitution test (DSST), and Stroop Color Word (Stroop) test were performed. Cerebral small vessel disease (SVD) was diagnosed as silent brain infarct and white matter lesions (WMLs) according to MRI. Results: Significantly stronger hippocampal and whole brain atrophy were observed in diabetic patients than non-diabetic subjects. The levels of glycosylated hemoglobin A1c were significantly correlated with indices of hippocampal and whole brain atrophy. In diabetic subjects, hippocampal atrophy was independently associated with age, albuminuria, serum intercellular adhesion molecules -1 levels and lower diastolic blood pressure, while whole brain atrophy was associated with age and subcortical WMLs grade. Regarding an association between albuminuria and brain atrophy, significant hippocampal and whole brain atrophy were found in patients with albuminuria after adjusting for confounders. Hippocampal atrophy was independently associated with word recall and Stroop test after adjustment, while whole brain atrophy was also associated with word recall, DSST, and Stroop test, although the association weakened after adding degree of SVD to the variables. Conclusions: Albuminuria was an independent risk factor for brain atrophy, especially hippocampal atrophy, which was associated with cognitive impairment, suggesting that the management of albuminuria may prevent progression of brain atrophy resulting in cognitive decline. In addition, the usefulness of VSRAD to support diagnosis of cognitive decline associated with brain atrophy was shown in daily clinical setting.

Quantification of Phase Values of Cerebral Microbleeds in Hypertensive Patients Using ESWAN MRI

The presence of cerebral microbleeds (CMBs) may have predictive and diagnostic value for cerebrovascular diseases. The purpose of our study was to measure the phase values (PVs) of CMBs by phase maps. We retrospectively analyzed 75 patients with hypertension who had CMBs using enhanced T2*-weighted angiography (ESWAN). The PVs of CMBs were measured and documented. The mean PVs of CMBs were correlated with demographic features and the grade of white matter lesions for seven brain regions. A total of 275 CMBs were found. Their mean PV was - 1.39 ± 0.29 radians. The mean PV of CMBs in seven brain regions was significantly lower than that of red nucleus and substantia nigra of healthy controls (P < .05). The mean PV of CMBs in the basal ganglia gray matter was significantly lower than that of the brainstem, subcortical white matter, and cerebellum (P < 0.05). In subcortical white matter, the PVs were significantly lower in patients with hypertension < 10 years than for those patients with hypertension ≥ 10 years (P < 0.05). In basal ganglia gray matter, the PVs were significantly lower in men than in women (P < 0.05). There was no significant correlation between the PVs of CMBs and the demographic features addressed or the grade of white matter lesions. Measurement of the PV of phase maps using ESWAN sequence provides quantitative information for detection of CMBs. The measurement data reported herein will provide a reference for a longitudinal study of CMBs in the future.

Chronic kidney disease, 24-h blood pressure and small vessel diseases are independently associated with cognitive impairment in lacunar infarct patients

Although the relationships between chronic kidney disease (CKD) and cognitive impairment (CI) have been highlighted, the etiology of CI in CKD remains uncertain. Subjects comprised 224 consecutive patients with symptomatic lacunar infarction who underwent magnetic resonance imaging and ambulatory blood pressure monitoring (ABPM). Diurnal blood pressure (BP) patterns were categorized into three groups: dippers, non-dippers and risers. Lacunar infarcts (LIs), including both symptomatic and silent and diffuse white matter lesions (WMLs), were graded into three grades according to their degree. The results of kidney function were evaluated using estimated glomerular filtration rate (eGFR), categorized into three groups: stage 1, >60; stage 2, 30-60; and stage 3, <30 ml min(-1) per 1.73 m(2). There were 44 patients with CI. Confluent WMLs, including WML 2 and WML 3, were found in 36 patients (81.8%), and multiple lacunae including LI 2 and LI 3 were found in 30 patients (68.1%) with CI. Age >75 years (odds ratio (OR), 5.5; P<0.05), male sex (OR, 2.8; P<0.05), non-dippers (OR, 6.3; P<0.05) and risers (OR, 5.6; P<0.05), eGFR 30-60 ml min(-1) per 1.73 m(2) (OR, 2.9; P<0.05) and eGFR <30 ml min(-1) per 1.73 m(2) (OR, 23.8; P<0.01), WML grade 2 (OR, 5.1; P<0.01) and WML grade 3 (OR, 45.2; P<0.001) and LI grade 2 (OR, 3.2; P<0.05) and LI grade 3 (OR, 6.4; P<0.05) were independently associated with CI. Age >75 years (OR, 4.1; P<0.05), eGFR 30-60 ml min(-1) per 1.73 m(2) (OR, 3.7; P<0.05) and eGFR <30 ml min(-1) per 1.73 m(2) (OR, 8.7; P<0.05) were independently associated with WML grade 3. Extensive small vessel diseases, CKD and non-dipping status were independently associated with CI. CKD appears to mainly contribute to vascular CI, whereas possibilities of overlapping with other mechanisms such as degenerative CI cannot be excluded. Strict night time BP control and renoprotective treatment may be warranted to prevent CI.

Does cerebral small vessel disease predict future decline of cognitive function in elderly people with type 2 diabetes?

Aims We conducted a 3-year longitudinal study concerning an association between cognitive function and cerebral small vessel disease (SVD) seen on magnetic resonance imaging (MRI) in elderly type 2 diabetic patients. Methods Four cognitive function tests – MMSE, word recall, Digit Symbol Substitution (DSS), and Stroop Color Word (Stroop) – were performed in 67 diabetic patients twice in 2006 and 2009. SVD was diagnosed as silent brain infarct (SBI) and white matter lesions (WMLs) according to MRI. Results Number of SBI was significantly correlated with a decline in DSS and Stroop tests, while WMLs grade was only associated with it in DSS tests after adjustment for age, gender, education years, the presence of hypertension and dyslipidemia, and smoking. Severity of SVD at baseline was stronger associated with cognitive function after the 3-year follow-up than at baseline. WMLs progression was associated with more rapid decline of DSS tests compared to a group without progression. Conclusions SVD seen on MRI is a good marker for predicting future cognitive decline, and monitoring of treatment through the use of such markers is expected to maintain a good quality of life for elderly diabetic patients.

Plasma Fibrinogen, Global Cognitive Function, and Cerebral Small Vessel Disease: Results of a Cross-Sectional Study in Community-Dwelling Japanese Elderly

Recent studies suggest that hemostatic and endothelial factors play a pivotal role in the development of cerebral small vessel disease (SVD). Although plasma fibrinogen is an essential factor in the coagulation cascade, the relationship among fibrinogen, cognitive function, and SVD has not been clarified in community-based Asian populations. Because fibrinogen levels of Asians have been reported to be lower than these of Caucasians, the impact of fibrinogen on the development of SVD or dementia in Asians may be different from that of Caucasians. We performed a cross-sectional study using MRI to determine the relationships among fibrinogen, cognitive function, and subclinical SVD in community-based Japanese elderly. Subjects with raised fibrinogen levels tended to have more lacunes and higher grades of white matter lesions (WMLs). Additionally, an independent association between fibrinogen and WMLs was determined by logistic regression analyses. Subjects with high fibrinogen levels accompanied by high von Willebrand factors or thrombomodulin levels had an increased tendency for the presence of WMLs. The relationship between the mean Mini-Mental State Examination (MMSE) scores and the quartiles of fibrinogen levels was not statistically significant after controlling for age, gender, and WMLs; however, the mean MMSE scores in subjects without WML were related to the tertiles of the fibrinogen levels even after adjusting for conventional risks and high sensitivity C-reactive protein. The present study suggests that there is a close relationship between fibrinogen levels and subclinical WMLs, which are independent of conventional risk factors and inflammation, in community-based Japanese elderly.

Small deep white matter lesions are associated with right-to-left shunts in migraineurs

The right-to-left shunts (RLS) and white matter lesions (WMLs) are frequently observed in migraineurs and in patients with ischemic stroke. Previous studies have reported that the burden of WMLs did not increase with the intracardiac right-to-left shunt (RLS) in migraineurs. However, some types of WMLs are known to be associated with RLS in patients with stroke and dementia. The aim of the study was to demonstrate the difference in the size and location of WMLs, according to the existence of RLS in patients with headache. From the prospective headache registry, a total of 425 subjects (age, 30.8 ± 5.1 years; 303 women; 242 migraineurs; 183 patients with tension-type headache (TTH)) were retrospectively reviewed and evaluated for RLS and WMLs using M-mode power transcranial Doppler sonography (mTCD) and brain magnetic resonance imaging scans. We scored WMLs, according to the Rotterdam Scan Study, and assessed the association between RLS presence and the location and size of WMLs. The number of small deep WMLs (dWMLs) and the prevalence of RLS, defined as microembolic signals (MES) ≥ 11, were higher in patients with migraine (small dWMLs, 6.23 vs. 4.05; RLS, 36.8% vs. 10.9%), compared to patients with TTH. There was no significant difference in the sum of periventricular WML grades or the total volume of dWMLs between TTH and migraine patients. Among the migraineurs, the patients with RLS more frequently had small dWMLs, aura, and heart disease compared to those without RLS. In addition, RLS were also independent predictors for the presence of small dWMLs from the multivariate binary regression analysis (p < 0.01; OR = 3.24; 95%CI 1.56-6.72). Small dWMLs are associated with RLS in young migraineurs. These results imply that paradoxical embolism may cause the small WMLs in some migraineurs.